CANCER MOLECULAR GENETICS PROGRAM: PROJECT SUMMARY/ABSTRACT The central theme of the Cancer Molecular Genetics (CMG) program is to identify and characterize the critical genes and genetic and epigenetic alterations that promote or suppress cancer initiation, progression, and therapeutic resistance, with the ultimate goal of translating this information to develop new strategies for more effective disease surveillance and more effective and less toxic treatments for cancers. The scientific goals of the program include the following: (1) identifying and functionally characterizing the key genes that contribute to cancer development by affecting immortalization, DNA synthesis, clonal dynamics, evasion of apoptosis and autophagy, invasion and metastasis, and angiogenesis; (2) determining the genetic and epigenetic mechanisms regulating expression of key genes in both normal and cancer cells; (3) identifying mechanisms by which genetic, epigenetic, and immunologic processes in cancer cells can be exploited to selectively induce cancer cell death; and (4) developing strategies for translating this knowledge into innovative approaches for the treatment of human cancers. The research projects addressing these goals fall into 2 major thematic areas, Tumorigenesis and Metastasis and Gene Expression and Epigenetics, and a third developing thematic area, Immunogenomics and the Tumor Microenvironment. Within each of these thematic areas, the scientific efforts are highly cancer-focused and range from basic discovery to translational and preclinical research. The CMG program has benefitted from a number of strategic recruitments over the past grant period, key among which is Seth Corey, MPH, MD, who has joined Jolene Windle, PhD, as co-leader of the program. The CMG program consists of a multidisciplinary group of 27 investigators from 11 academic departments representing 4 schools. The program has a funding base of over $3.8 million in annual direct costs, of which more than $1.3 million is from the NCI. CMG program members have many well-established and productive collaborations, which have resulted in multiple jointly funded research initiatives and high-impact publications. Half of the 400 publications from CMG program members in 2011-2015 involved collaborations with other Massey Cancer Center members (including greater than one-third with intraprogrammatic and one-third with interprogrammatic collaborations). In addition, greater than half involved interinstitutional collaborations. The CMG program provides a highly interactive and collaborative research environment that facilitates scientific exchange within the program and with members of other programs. The CMG program is also strongly committed to mentorship of its junior faculty members, postdoctoral fellows, and doctoral students to train the next generation of cancer biologists and therapists. Through these efforts, the CMG program creates a synergistic environment that promotes the success of its members to advance our scientific understanding of cancer and translate these advances into more effective preventative and therapeutic measures.